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61.
Clint L. Miller Amy R. Kontorovich Ke Hao Lijiang Ma Conrad Iyegbe Johan L.M. Björkegren Jason C. Kovacic 《Journal of the American College of Cardiology》2021,77(20):2531-2550
In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types. 相似文献
62.
目的探讨乳腺浸润性导管癌中雌激素调节蛋白(PS2)的表达及其与雌激素受体(ER)、孕激素受体(PR)的关系。方法收集新疆医科大学附属肿瘤医院2008-2009年经病理确诊并行外科手术治疗的70例乳腺浸润性导管癌组织石蜡标本,采用免疫组化法检测PS2、ER、PR表达,分析PS2与ER、PR表达及临床病理因素的相关关系。结果 PS2、ER、PR阳性表达率分别为37.14%(26/70)、40.00%(28/70)、42.86%(30/70)。PS2在ER阳性和阴性病例中的阳性表达率分别为60.71%(17/28)和21.43%(9/42),两者差异有统计学意义(P<0.05)。PS2在PR阳性和阴性病例中的阳性表达率分别为66.67%(20/30)和15.00%(6/40),两者差异有统计学意义(P<0.05)。患者年龄、月经状态与PS2蛋白表达无明显关系(P>0.05),PS2表达与ER呈正相关(γs=0.35,P=0.014),PS2表达与PR呈正相关(γs=0.475,P=0.000),PS2表达与患者组织分级及淋巴结转移有关(P<0.05)。结论 PS2表达与ER、PR及淋巴结转移状况与组织分级临床因素有关。ER、PR、PS2综合检测对判定乳腺内分泌治疗效果及预后具有重要意义。 相似文献
63.
目的:探讨磷脂酶A2-ⅡA(PLA2-ⅡA)在直肠癌患者中的表达和临床意义.方法:采用免疫组化检测45例直肠癌标本、34例基本正常的直肠黏膜、32例直肠腺瘤组织中PLA2-ⅡA的表达水平,并观察PLA2-ⅡA表达水平与临床病理特征之间的关系.结果:直肠癌组PLA2-ⅡA表达水平明显高于直肠腺瘤组、正常组,差异有统计学意义(P<0.05);直肠腺瘤组PLA2-ⅡA表达水平高于正常组,但差异无统计学意义(P=0.677);PLA2-ⅡA阳性表达水平随着肿瘤浸润程度加重、分化程度降低、TNM分期升高、脉管侵犯而明显降低,差异有统计学意义(P<0.05).结论:PLA2-ⅡA在直肠癌癌组织中高表达,与肿瘤浸润程度、分化程度、TNM分期、脉管是否侵犯、神经束是否侵犯有关,其可能在直肠癌的发生、发展中起重要的作用. 相似文献
64.
David P. Steensma 《Mayo Clinic proceedings. Mayo Clinic》2018,93(8):1122-1130
Clonal hematopoiesis (CH)—an expansion of blood cells derived from a single hematopoietic stem cell—is a defining feature of hematologic cancers, but recently CH was also found to be a frequent consequence of aging. When aging-associated CH results from acquisition of a somatic mutation in a driver gene associated with leukemia, and this mutation is present at a variant allele frequency of at least 0.02 (2%) yet the patient does not meet World Health Organization diagnostic criteria for a hematologic neoplasm, this state is termed clonal hematopoiesis of indeterminate potential (CHIP). CHIP is present in approximately 10% to 15% of people older than 70 years and more than 30% by age 85 years and represents a precursor state for neoplasia akin to monoclonal gammopathy of undetermined significance. Recently, CHIP was unexpectedly found to be an important risk factor for cardiovascular events, with accumulating evidence supporting a mechanism of accelerated atherogenesis as a result of vascular inflammation driven by clonally derived monocytes/macrophages. Risk factors for CHIP include aging, male sex, cigarette smoking, and a common germline variant in the telomere-associated gene TERT. Clonal hematopoiesis can also occur after cytotoxic chemotherapy or radiotherapy for a solid tumor, after hematopoietic stem cell transplant, in the context of aplastic anemia, or after induction chemotherapy for acute leukemia; in each setting, CH has distinct clinical implications. This review summarizes recent studies of CH and CHIP and outlines challenges in clinical management of affected patients. 相似文献
65.
目的 探讨肝衰竭患者发生急性胰腺炎(AP)的危险因素.方法 回顾性分析成都医学院第一附属医院2009年6月至2013年6月收治的140例肝衰竭患者的临床资料,通过x2检验分别比较在不同情况下肝衰竭AP发病率的差异,经单因素分析后选取P<0.05的因素进行多因素Logistic回归分析.结果 单因素分析显示,呕吐症状、直接胆红素/总胆红素(CB/TB)、血清钠、血脂、胆石症、并发症个数、糖皮质激素、人工肝治疗存在统计学差畀(P<0.05),多因素Logistic回归分析显示,呕吐症状、胆石症、并发症个数、糖皮质激素差异有统计学意义(P<0.05).结论 呕吐症状、胆石症、并发症个数、应用糖皮质激素是肝衰竭患者发生AP的危险因素. 相似文献
66.
67.
目的:探讨人乳头瘤病毒(HPV)E6/E7mRNA检测用于未明确诊断意义的不典型鳞状上皮细胞(ASCUS)诊断结果的判定价值。方法:对160例薄层液基细胞学检查诊断为ASCUS者进行HPV E6/E7mRNA和高危型HPV(HR-HPV)DNA检测,结合病理学诊断资料进行统计学分析。结果:160例中病理结果为宫颈上皮内瘤变Ⅱ级(CINⅡ)及以上级别者的HPV E6/E7mRNA阳性率明显高于CINⅡ以下级别者,差异有统计学意义(P0.05),但与HR-HPV DNA检测结果无统计学差异。HPV E6/E7 mRNA检测CINII及以上级别的灵敏度(69.2%)与HR-HPV DNA检测相比无统计学差异(P0.05);特异度(73.9%)高于HR-HPV DNA检测(61.9%),差异有统计学意义(P0.05)。结论:HPV E6/E7 mRNA检测可作为ASCUS者是否需要进行阴道镜检查的一项指标依据。 相似文献
68.
Summary There are a number of systems for diagnosing multiple myeloma, myeloma variants and monoclonal gammopathy of undetermined significance. We compared three systems, those according to Durie and Salmon, to Kyle and Greipp, and to the British Columbia Cancer Agency, using material from a populationbased registry of 847 patients with a paraproteinemia or multiple myeloma. Of these, 157 underwent both bone marrow and X-ray examinations and were subsequently included in our analysis. The differences between the systems were small, even though in only 64% of the cases the diagnosis according to all three systems was identical. The system used by the British Columbia Cancer Agency turned out to be the shortest and easiest system reviewed here. We propose a more frequent application of this system instead of the more commonly used Durie and Salmon and Kyle and Greipp criteria. 相似文献
69.
Sati HI Greaves M Apperley JF Russell RG Croucher PI 《British journal of haematology》1999,104(2):350-357
Interleukin-1beta(IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are potent bone resorbing cytokines that may contribute to the development of the osteolytic bone disease observed in patients with multiple myeloma (MM). Although these factors have been identified in cultures of bone marrow mononuclear cells isolated from patients, the identity of the cells responsible for producing IL-1beta and TNFalpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (FISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1beta and TNFalpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1beta and TNFalpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined. In contrast, the TNFalpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1beta and TNFalpha mRNA and proteins were readily detected within a small proportion of the non-plasma cells from patients with both MM and MGUS. These data suggest that myeloma cells in vivo are able to produce TNFalpha but not IL-1beta. In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both ILbeta and TNFalpha. 相似文献
70.
Politou M Terpos E Anagnostopoulos A Szydlo R Laffan M Layton M Apperley JF Dimopoulos MA Rahemtulla A 《British journal of haematology》2004,126(5):686-689
The aim of this study was to evaluate the role of markers of bone remodelling, and osteoclast activation/function in patients with monoclonal gammopathy of undetermined significance (MGUS). We have measured serum levels of soluble RANKL (sRANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alpha), markers of bone resorption [N-telopeptide of collagen type-I (NTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)] and bone formation [bone-alkaline phosphatase (bALP)] in 40 MGUS patients. These parameters were compared with those of 42 newly diagnosed myeloma patients, and 45 healthy, gender- and age-matched controls. MGUS patients had elevated levels of NTX, sRANKL, and sRANKL/OPG ratio compared with controls (P < 0.0001). Furthermore, TRACP-5b, MIP-1alpha and NTX were decreased in patients with MGUS compared with myeloma patients (P < 0.001), while OPG and bALP were increased (P < 0.001). Serum levels of MIP-1alpha, as well as TRACP-5b, and sRANKL/OPG ratio were reduced, while bALP was increased in MGUS patients, even when compared with myeloma patients who had stage I/II disease. These results demonstrate that increased osteoclastogenesis leading to increased bone resorption is present in MGUS but seems to be compensated for by normal bone formation, which is absent in MM. Furthermore MIP-1alpha, bALP, and sRANKL/OPG may be useful tools for distinguishing between cases of MGUS and early myeloma. 相似文献